Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Vernal, Sebastian; Brochado, Maria Jose Franco; Bueno-Filho, Roberto; Louzada-Junior, Paulo; Roselino, Ana Maria

doi:10.1590/0037-8682-0216-2017

Short Communication • Rev. Soc. Bras. Med. Trop. 51 (01) • Jan-Feb 2018 • https://doi.org/10.1590/0037-8682-0216-2017 linkcopy

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Authorship SCIMAGO INSTITUTIONS RANKINGS

INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE.

METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden’s factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed.

RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation.

CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Keywords:
Leprosy; Antiphospholipid antibodies; Beta-2-glycoprotein-I; Factor V Leiden; Prothrombin; Thromboembolism

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7
Age (years)	45	54	26	69	31	48	70
Sex	Male	Male	Female	Male	Male	Male	Male
Ethnicity	Caucasian	Caucasian	Caucasian	Mulatto	Caucasian	Caucasian	Caucasian
Ridley-Jopling Classification (Date)	LL (12.1997)	BL (10.2002)	LL (04.2000)	BB (01.2004)	BL (12.2003)	BL (07.2001)	BL (06.2006)
Leprosy immune reaction	TR2	TR2	TR2	None	TR2	TR2	TR1
Bacilloscopy	Positive	Positive	Positive	Negative	Positive	Positive	Positive
Thrombotic episode (Date)	DVT in RL (03.1999)	DVT in LL PE in Left Lung (both lobes) (01.2003 & 03. 2004)	PTE (06.2003)	DVT in RL PTE bilateral (01.2004)	DVT in RL (04.2004)	DVT in LL (09.2004)	DVT in LL PTE (05.2007)
Use of thalidomide and/or corticosteroids during the thrombotic episode	Both	Both	Both	No	Both	Both	Prednisone
Prescription of MDT during the thrombotic episode	Yes	Yes	No	Yes	Yes	No	Yes

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7
(Date) IgM anti-PGL1 (index) (NV < 1.0)	(09.2000) 0.3	(10.2002) 25.0	(05.2000) 1.7	(03.2005) 0.8	(01.2004) 1.5	(07.2001) 26.8	(01.2006) 0.5
	(04.2005) 0.5	(03.2004) 1.5	(04.2002) 1.0			(10.2004) 1.8	(12.2006) 0.4
		(09.2004) 4.6	(05.2002) 0.5			(11.2004) 1.5
(Date) IgG aCL (GPL) (NV < 15)	(04.2004) <15	(01.2004) 35.0	(06.1999) <15	(03.2005) <15	(04.2004) 44.0	(04.2005) <15	(05.2007) <15
	(04.2005) <15	(08.2004) 32.0	(04.2001) 9.0	(04.2005) 16.3	09.2004) <15	(06.2005) <15
		(09.2004) 34.0	(05.2001) <15	(07.2005) 18.8	(06.2005) <15
			(08.2004) <15
			(10.2004) <15
(Date) IgM aCL (MPL) (NV < 12.5)	(04.2004) <12.5	(01.2004) 25.0	(01.2001) 12.5	(03.2005) <12.5	(04.2004) 34.0	(04.2005) <12.5	(05.2007) <12.5
	(04.2005) <12.5	(08.2004) 85.0	(05.2001) 70.0	(04.2005) <12.5	(08.2004) <12.5	(06.2005) <12.5
		(09.2004) 94.0	(08.2004) 54.0	(07.2005) <12.5	(06.2005) <12.5
			(10.2004) 68.0
(Date) Lupus anticoagulants	(04.2004) (-)	Not done	(09.2005) (+)	(07.2005) (-)	Not done	(09.2004) (-)	Not done
	(06.2005) (+)					(04.2005) (-)
	(12.2005) (+)					(06.2005) (+)
						(09.2005) (+)
(Date) IgG anti - ß2GPI (SMU) (NV < 10)	(09.2005) <10	(09.2005) <10	(09.2005) <10	(09.2005) <10	(09.2005) >100	(09.2005) <10	(05.2007) <10
(Date) IgM anti-ß2GPI (NV < 12)	(09.2005) <12	(09.2005) <12	(09.2005) >100	(09.2005) <12	(09.2005) >100	(09.2005) <12	(05.2007) <12
Anti-thrombin III (NV 70-130%)	107	73	86	101	Not done	114	Not done
Protein C (NV 70-130%)	150	Not done	115	68	Not done	128	Not done
Protein S (NV 50-130%)	70	Not done	88	Not done	Not done	95	Not done
Kaolin clotting time	Negative	Positive	Negative	Negative	Not done	Positive	Not done
Fibrinogen (mg/dL) (NV 200-400)	Not done	394	326	800	Not done	454	Not done
Factor V Leiden (NV +/+)	+/+	+/+	+/+	+/+	+/+	+/+	+/+
Prothrombin G20210A mutation (NV -/-)	-/-	-/-	-/-	+/-	-/-	-/-	-/-
ß2GPI Leu247Val Polymorphism	Heterozygote (Haplotype 1&4)	Heterozygote (Haplotype 1&4)	Homozygote Val/Val (Haplotype 4)	Heterozygote (Haplotype 1&4)	Heterozygote (Haplotype 1&4)	Homozygote Val/Val (Haplotype 4)	Homozygote Val/Val (Haplotype 4&7)

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[TFN1] LL: Lepromatous leprosy; BL: borderline leprosy; BB: borderline-borderline leprosy; TR1: leprosy reaction type 1; TR2: leprosy reaction type 2; DVT: deep venous thrombosis; RL: right leg; LL: left leg; PTE: pulmonary thromboembolism; MDT: multi-drug treatment.